Group A streptococcal infections cause a wide array of clinical syndromes, ranging from uncomplicated pharyngitis and pyoderma to serious, invasive infections and toxic shock syndrome. Protection against infection is largely mediated by antibodies against the surface M protein of the organisms. M protein is an alpha-helical, coiled-coil molecule that extends from the surface with its hypervariable N-terminus exposed to the outside and the conserved C-terminus buried in the cytoplasm. The N-terminus contains type-specific epitopes that evoke bactericidal antibodies that correlate with protection against the homologous serotype. The emm gene is located in a regulon that is controlled by the upstream positive regulator mga. Depending on the serotype, the regulon may contain one, two or three emm and emm-like genes. In serotypes containing only one emm gene, deletion or interruption of the emm gene results in an avirulent organism that can no longer resist phagocytosis. In serotypes that express several emm-like genes, each may partially contribute to resistance to phagocytosis, but among the many defined surface proteins of group A Streptococci, only antibodies against the M protein have been shown to be opsonic.
Understanding the molecular basis of non-M protein mediated cross serotype protection would aid in providing therapeutic treatments for a variety of infections cause by group A streptococci. Type 18 Streptococci have been identified as an important serotype in the resurgence of acute rheumatic fever in Utah. In addition, Types 3 and 18, and to a lesser extent Type 28 Streptococci have all been implicated in the recent resurgence of serious Streptococcal diseases. Each of these diseases could be potentially be prevented by vaccination with an antigen other than M protein, which is capable of eliciting a protective response across divergent serotypes.
Presently, there appears to be no showing in the art that group A streptococci (and all that follow-group A streptococci) express surface polypeptides or proteins containing opsonic epitopes not related to M protein. Providing polypeptides from Streptococci containing non-M protein antigens, especially those that have opsonic epitopes would enhance therapeutic tools available to protect against a variety of Streptococcal infections.
Therefore, there is a need in the art for the discovery and characterization of non-M protein antigens which are effective for protecting against such infections, especially antigens that are effective against multiple serotypes of group A Streptococci.